Early Activation of FGF and Nodal Pathways Mediates Cardiac Specification Independently of Wntβ-Catenin Signaling 英文参考文献.docVIP

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Early Activation of FGF and Nodal Pathways Mediates Cardiac Specification Independently of Wntβ-Catenin Signaling 英文参考文献.doc

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Early Activation of FGF and Nodal Pathways Mediates Cardiac Specification Independently of Wntβ-Catenin Signaling 英文参考文献

EarlyActivationofFGFandNodalPathwaysMediates CardiacSpecificationIndependentlyofWnt/b-Catenin Signaling LeeJ.Samuel,BrankoV.Latinkic′* SchoolofBiosciences,CardiffUniversity,Cardiff,UnitedKingdom Abstract Background: Cardiac induction, thefirst step in heart development in vertebrate embryos, is thought to be initiatedby anteriorendodermduringgastrulation,butwhatthesignalsareandhowtheyactisunknown.Severalsignalingpathways, including FGF, Nodal, BMP and Wnt have been implicated in cardiac specification, in both gain- and loss-of-function experiments. However, as these pathways regulate germ layer formation and patterning, their specific roles in cardiac inductionhavebeendifficulttodefine. Methodology/PrincipalFindings:Toinvestigatethemechanismsofcardiacinductiondirectlywedevisedanassaybased on conjugates of anterior endoderm from early gastrula stage Xenopus embryos as the inducing tissue and pluripotent ectodermalexplantsastherespondingtissue.Weshowthattheanteriorendodermproducesaspecificsignal,asskeletal muscleisnotinduced.Cardiacinducingsignalneedsuptotwohoursofinteractionwiththerespondingtissuetoproduce an effect. While we found that the BMP pathway was not necessary, our results demonstrate that the FGF and Nodal pathwaysareessentialforcardiogenesis.Theywererequiredonlyduringthefirsthourofcardiogenesis,whilesustained activationofERKwasrequiredforatleastfourhours.OurresultsalsoshowthattransientearlyactivationoftheWnt/b- cateninpathwayhasnoeffectoncardiogenesis,whilelateractivationofthepathwayantagonizescardiacdifferentiation. Conclusions/Significance:Wehavedescribedanassayforinvestigatingthemechanismsofcardiacinductionbyanterior endoderm.Theassaywasusedtoprovideevidenceforadirect,earlyandtransientrequirementofFGFandNodalpathways. Inaddition,wedemonstratethatWnt/b-cateninpathwayplaysnodirectroleinvertebratecardiacspecification,butneeds tobesuppressedjustpriortodifferentiation. Citation: Samuel LJ, Latinkic′ BV (2009) Early Activation of FGF and Nodal Pathways Med